Can be acquired (e.g., liver disease) or hereditary(e.g., urea cycle enzyme deficiencies).Results in excess NH4+, which depletes α-ketoglutarate, leading to inhibition of TCA cycle.

Hyperammonemia Treatment:

limit protein in diet. Benzoate or phenylbutyrate (both of which bind amino acid and lead to excretion) may be given to dec ammonia levels. Lactulose to acidify the GI tract and trap NH4+ for excretion.

Most common urea cycle disorder. X-linked recessive (vs. other urea cycle enzyme deficiencies,which are autosomal recessive). Interferes with the body’s ability to eliminate ammonia. Often evident in the first few days of life, but may present with late onset. Excess carbamoyl phosphate isconverted to orotic acid (part of the pyrimidine synthesis pathway).

Hereditary defect of renal PCT and intestinal amino acid transporter for Cysteine, Ornithine,Lysine, and Arginine (COLA).Excess cystine in the urine can lead to precipitation of hexagonal cystine stones.

In the liver, fatty acids and amino acids are metabolized to acetoacetate and β-hydroxybutyrate (to be used in muscle and brain). In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis. In alcoholism, excess NADH shuntsoxaloacetate to malate. Both processes cause a buildup of acetyl-CoA, which shunts glucose and FFA toward the production of ketone bodies.

Rate-limiting step in Cholesterol synthesis

HMG-CoA reductase (induced by insulin), which converts HMG-CoA to mevalonate.

Lipid transport, key enzymes
6 of them

1- Pancreatic lipase—degradation of dietary triglycerides (TG) in small intestine.

2-Lipoprotein lipase (LPL)—degradation of TG circulating in chylomicrons and VLDLs. Found on vascular endothelial surface.

Lipoproteins are composed of varying proportions of cholesterol, TGs, and phospholipids. LDL and HDL carry most cholesterol. LDL transports cholesterol from liver to tissues. HDL transports cholesterol from periphery to liver.

Chylomicron

Delivers dietary TGs to peripheral tissue. Delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their triacylglycerols. Secreted by intestinal epithelial cells.

VLDL

Delivers hepatic TGs to peripheral tissue. Secreted by liver.

IDL

Formed in the degradation of VLDL. Delivers TGs and cholesterol to liver.

LDL

Delivers hepatic cholesterolto peripheral tissues. Formed by hepatic lipase modification of IDL in the peripheral tissue. Taken up by target cells via receptor-mediated endocytosis.

HDL

Mediates reverse cholesterol transport from periphery to liver. Acts as a repository for apoC and apoE (which are needed for chylomicron and VLDL metabolism). Secreted from both liver and intestine. Alcohol inc. synthesis.